The three-dimensional structures of methotrexate, dichloromethotrexate, aminopterin, folinic acid and quinazoline analogues of folic acid and of methotrexate will be determined by X-ray crystallography. From a comparison of these compounds' stereochemical similarities and differences, we will design new potential folate-antagonist anticancer agents. Structural studies will be made on two other classes of cancer chemotherapy drugs: ICRF-159 and its conformationally fixed analogues, and cyclophosphamide derivatives. The goal of these studies is to identify stereochemical parameters for these compounds that are related to the drugs' anticancer activity and thus to be able to suggest guidelines for design of better drugs in these classes as well as to learn more about their mechanisms of action. We will also carry out crystallographic investigations of the structures of deoxyribodinucleotides, the molecular subunits of DNA.